Vacuolar fusion protein MON1 homolog A (MON1A)
The protein contains 652 amino acids for an estimated molecular weight of 72895 Da.
Plays an important role in membrane trafficking through the secretory apparatus. Not involved in endocytic trafficking to lysosomes (By similarity). Acts in concert with CCZ1, as a guanine exchange factor (GEF) for RAB7, promotes the exchange of GDP to GTP, converting it from an inactive GDP-bound form into an active GTP-bound form (PubMed:23084991). (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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The reference OMIM entry for this protein is 611464
Mon1, s. cerevisiae, homolog of, a; mon1a
Sand1
CLONING
Wang et al. (2007) identified 2 splice variants of mouse Mon1a that differed in the inclusion or exclusion of 3-prime exons. Western blot analysis detected a 60- to 65-kD protein in all mouse issues examined. By database analysis, Wang et al. (2007) identified MON1A in human and several other species.GENE FUNCTION
Using primary mouse macrophages, Wang et al. (2007) found that knockdown of Mon1a with small interfering RNA (siRNA) led to the intracellular accumulation of ferroportin (SLC40A1; 604653) and the absence of ferroportin at the cell surface. Knockdown of Mon1a had no effect on iron loading, but inhibited iron release. Inhibition of Mon1a also prevented lipopolysaccharide (LPS)-induced expression of MHC class II molecules on the cell surface and the secretion of interleukin-6 (IL6; 147620) and Il12 (see 161560). Knockdown of mouse Mon1a interrupted trafficking through the secretory apparatus without affecting endocytic trafficking to lysosomes or the size and distribution of lysosomes. Kinchen and Ravichandran (2010) used genetic, cell biologic, and molecular studies in C. elegans and mammalian cells to identify SAND1 and its partner CCZ1 as factors in corpse removal. In worms deficient in either sand1 or ccz1, apoptotic cells were internalized and the phagosomes recruited the small GTPase Rab5 (179512) but failed to progress to the subsequent Rab7 (602298)-positive stage. The mammalian orthologs of SAND1, namely MON1A (611464) and MON1B (608954), were similarly required for phagosome maturation. Mechanistically, Mon1 interacts with GTP-bound Rab5, identifying Mon1 as a previously unrecognized Rab5 effector. Moreover, a Mon1-Ccz1 complex (but neither protein alone) could bind Rab7 and could also influence Rab7 activation, suggesting Mon1-Ccz1 as an important link in progression from the Rab5-positive stage to the Rab7-positive stage of phagosome maturation. Taken together, Kinchen and Ravichandran (2010) concluded that these data identified SAND1 and CCZ1 as critical and evolutionarily conserved components regulating the processing of ingested apoptotic cell corpses.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the MON1A gene to chromosome 3 (TMAP WI-19760). Wang et al. (2007) mapped the mouse Mon1a gene to chromosome 9.ANIMAL MODEL
Wang et al. (2007) found that C57BL strains of mice had much lower spleen iron content than all other strains, and that this was due to an N374S substitution in the Mon1a protein. Asparagine in this position (N373 in humans) is conserved in all species examined except insects. ... More on the omim web site
Feb. 23, 2019: Protein entry updated
Automatic update: model status changed
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 611464 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).